Project start date: 01-Dec-2023 Project end date: 30-Nov-2025

SCN1A Horizons: A natural history study of SCN1A-related epilepsies in the UK

Case Definitions: A child or adult with a diagnosis of epilepsy who has undergone genetic testing and has a confirmed pathogenic SCN1A variant.

Age range for cases: 0 months – adulthood

Investigators and Contact Details: Enquiry contact details:

Dr Kirsty Hendry
Research Study Coordinator
University Of Glasgow
Email address: kirsty.hendry@glasgow.ac.uk

Inclusion Criteria: Patients meeting the following criteria will be considered eligible for this study:
1. Patient and/or legally authorised representative must be willing and able to give informed consent/assent for participation in the study.
2. Patient and their parent/caregiver are willing and able (in the Investigator’s opinion) to comply with all study requirements (including ability and willingness to comply with virtual visits).
3. Participant has a confirmed pathogenic (class 5) or likely pathogenic (class 4) SCN1A variant, as demonstrated by genetic testing.
* Please note, patients participating in other research studies or trials may still take part in this study which does not administer any investigational medicinal products.

Exclusion Criteria: 1. Patient has any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or may affect the patient’s ability to participate in the study.

Additional Information:

 

Chief investigator:
Prof Andreas Brunklaus
Consultant Paediatric Neurologist
Royal Hospital For Children Glasgow
Email: andreas.brunklaus@glasgow.ac.uk

Outcomes:

Expected numbers:

Estimated 40-60 new diagnoses per year.

This estimate is based on findings from a prospective, population-based national cohort which found SCN1A-related epilepsies in 1 per 12,200 births. Based on official figures released by the Office for National Statistics, the UK live birth rate was 681,560. This would equate to approximately 56 cases of SCN1A-related epilepsies.

Source of denominator data:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658850/

https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimat es/datasets/vitalstatisticspopulationandhealthreferencetables


Ethical approval Notification of cases:
Ethical approval has been obtained.
Scotland REC reference – 22/SS/0072
England/Wales REC reference – 22/WA/0117
Amendment SA 03 included an amendment to allow for identification of participants via BPNSU (detail added to Protocol v2.0).


Methods:
We will systematically collect longitudinal validated outcome measures for SCN1A variantcarrying patients across the UK. This will be done ensuring that data collected are not only clinically meaningful, but also sufficiently robust for use in clinical research. We will benefit from the uniformity of assessment that having a single UK National Health Service (NHS) allows.

The study participants will have two different types of standardized assessments: a clinical standard of care assessment and a neuropsychology assessment. Clinical assessments will be conducted 6-monthly as part of the patient’s routine clinical care. Neuropsychology assessments will be performed either 6-monthly or yearly (according to age) and include detailed neurocognitive and comorbidity evaluations. The study will employ 4 trained fulltime Paediatric Neuropsychology Research Assistants (RAs) located across the UK to carry out all neuropsychological assessment visits. A total of 300 participants will complete both clinical standard of care as well as neuropsychological assessment visits. A further sub-set of up to 100 participants will complete clinical standard of care visits only.

Recruitment will be stratified by age and patients will be followed-up over a period of 3 years (recruitment will be phased out over 4 years):
· 30 patients per year age 0 to 2 years old (n = 80)
· 20 patients per year age 3 to 6 years old (n = 120)
· 10 patients per year age 7 to 16 years old (n = 140)
· 60 adult patients.

Alternative sources of data
Participants will be identified by qualified research staff. This may be done from current lists of potential patients at clinics or using databases. Identification may involve a disease register, computerised search or review of medical records. The identification of patients will primarily be done by the direct healthcare team, however external referrals are a possibility from any potential clinician/GP that have heard about the study (i.e. referral) and believes that he/she has a potentially eligible patient. The study is also supported by the charity Dravet Syndrome UK who will develop communication content to be shared through their website which we anticipate will reach families of people with Dravet Syndrome as well as healthcare providers. A central email address and study team phone number will be provided for enquiries.


Questionnaire
All study questionnaires are reviewed and piloted among clinical study teams.


Funding arrangements
This is an investigator led study sponsored by NHS Greater Glasgow and Clyde. The study is funded via a combination of industry and charity grant funding. The industry funders are Biocodex, Encoded Therapeutics Inc., Jazz/GW Pharmaceuticals, Stoke Therapeutics Inc. and UCB/Zognenix Inc. Charity grant funding has been awarded by Dravet Syndrome UK and Dravet Syndrome Foundation.